Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement.

Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Intensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock. METHODS AND ANALYSIS: We will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay. ETHICS AND DISSEMINATION: Ethics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials. PROSPERO REGISTRATION NUMBER: CRD42021260375.

LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial.

BACKGROUND: Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited. METHODS: The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions. DISCUSSION: LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021.

Protocol summary and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial.

Background: Targeted therapeutic mild hypercapnia may attenuate brain injury in comatose adults resuscitated from out-of-hospital cardiac arrest. Objective: To describe the study protocol and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial. Design, setting, participants and interventions: TAME is a phase 3, multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial that will be conducted in intensive care units in Australia, Canada, Ireland, Saudi Arabia, New Zealand, Scandinavia, Singapore, Central and Western Europe, and the United Kingdom. A total of 1700 comatose adults resuscitated from out-of-hospital cardiac arrest will be randomly assigned to 24 hours of targeted therapeutic mild hypercapnia (arterial carbon dioxide tension 50-55 mmHg) or targeted normocapnia (arterial carbon dioxide tension 35-45 mmHg) in a 1:1 ratio. TAME recruitment began in March 2018 and is expected to be complete in September 2021. Main outcome measures: The primary outcome measure is the proportion of participants with a favourable functional outcome at 6 months. Functional outcomes will be assessed using the Glasgow Outcome Scale-Extended (GOSE); this scale ranges from 1 to 8, with a higher value indicating a better outcome. We will define participants with a GOSE of 5 to 8 as having a favourable functional outcome. Secondary outcomes include 6-month mortality, cognitive function and quality of life. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: TAME will compare the effect of targeted therapeutic mild hypercapnia versus targeted normocapnia on functional outcomes in adults resuscitated from out-of-hospital cardiac arrest who are admitted to an intensive care unit. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12617000036314p) and ClinicalTrials.gov (NCT03114033).

Patient-centred and family-centred care of critically ill patients who are potential organ donors: a qualitative study protocol of family member perspectives.

INTRODUCTION: In a patient-centred and family-centred approach to organ donation, compassion is paramount. Recent guidelines have called for more research, interventions and approaches aimed at improving and supporting the families of critically ill patients. The objective of this study is to help translate patient-centred and family-centred care into practice in deceased organ donation. METHODS AND ANALYSIS: This will be a national, qualitative study of family members of deceased organ donors in Canada. We will include family members who had been approached regarding an organ donation decision, including those who agreed and declined, at least 2 months and no later than 3 years after the patients' death. Data collection and analysis is ongoing and will continue until September 2020 to include approximately 250 participants. Family members will be identified and recruited from provincial organ donation organisation databases. Four experienced qualitative researchers will conduct telephone interviews in English or French with audio-recording for subsequent transcription. The research team will develop a codebook iteratively through this process using inductive methods, thus generating themes directly from the dataset. ETHICS AND DISSEMINATION: Local research ethics boards (REB) at all participating sites across Canada have approved this protocol. The main REB involved is the Ottawa Health Science Network REB. Data collection began in August 2018. Publication of results is anticipated in 2021. Study findings will help improve healthcare provider competency in caring for potential organ donors and their families and improve organ donation consent rates. Findings will also help with the development of educational materials for a competency-based curriculum for critical care residents.

Predicting Performance Status 1 Year After Critical Illness in Patients 80 Years or Older: Development of a Multivariable Clinical Prediction Model.

OBJECTIVE: We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU. DESIGN: Prospective, longitudinal cohort study. SETTING: Twenty-two Canadian ICUs. PATIENTS: We recruited 527 patients 80 years or older who had a medical or urgent surgical diagnosis and were admitted to an ICU for at least 24 hours. MEASUREMENTS AND MAIN RESULTS: At baseline, we completed a comprehensive geriatric assessment of enrolled patients; survival and functional status was determined 12 months later. We defined recovery from critical illness as Palliative Performance Scale score of greater than or equal to 60. We used logistic regression analysis to examine factors associated with this outcome. Of the 434 patients (82%) whose Palliative Performance Scale was known at 12 months, 50% had died and 29% (126/434) had a score of greater than or equal to 60. In the multivariable model, we found that being married, having a primary diagnosis of emergency coronary artery bypass grafting or valve replacement, and higher baseline Palliative Performance Scale were independently predictive of a 12-month Palliative Performance Scale score of greater than or equal to 60. Male sex, primary diagnosis of stroke, and higher Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, or clinical frailty scale were independently predictive of Palliative Performance Scale score of less than 60. CONCLUSION: Approximately one-quarter of very old ICU patients achieve a reasonable level of function 1 year after admission. This prediction model applied to individual patients may be helpful in decision making about the utility of life support for very elderly patients who are admitted to the ICU.

Recovery after critical illness in patients aged 80 years or older: a multi-center prospective observational cohort study.

PURPOSE: Increasingly, very old patients are admitted to Intensive Care Units (ICUs). The objective of this study was to describe 12-month outcomes of these patients and determine which characteristics are associated with a return to baseline physical function 1 year later. METHODS: In this prospective cohort study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older who were admitted to ICU for at least 24 h. At baseline, we completed a comprehensive geriatric assessment and followed patients to determine 12-month survival and physical function. Our primary outcome was physical recovery from critical illness at 12 months, defined as being alive with Short Form-36 physical function score of at least 10 points, and not 10 or more points below baseline. We used regression analysis to examine factors associated with physical recovery. RESULTS: Patients were on average 84 years old (range 80-99). Mortality was 14% in ICU, 26% in hospital and 44% at 12 months after admission. Of 505 patients evaluable at 12 months, 26% achieved physical recovery. In the multivariable model, physical recovery was significantly associated with younger age, lower APACHE II score, lower Charlson comorbidity score, lower frailty index, lower baseline physical function score, and specific admission diagnoses. CONCLUSIONS: One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year. Routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients. (ClinicalTrials.gov number NCT01293708).

The Very Elderly Admitted to ICU: A Quality Finish?

OBJECTIVE: Very elderly persons admitted to ICUs are at high risk of death. To document life-sustaining interventions (mechanical ventilation, vasopressors, renal replacement therapy) provided in the ICU and outcomes of care. DESIGN: Multicenter, prospective cohort study. SETTING: ICUs of 24 Canadian hospitals. PARTICIPANTS/SETTING: Patients 80 years old or older admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand six hundred seventy-one patients were included. The average age of the cohort was 85 years (range, 80-100 yr). Median total length of stay in ICU was 4 days (interquartile range, 2-8 d) and in hospital was 17 days (interquartile range, 8-33 d). Of all patients included, 502 (30%) stayed in ICU for 7 days or more and 344 (21%) received some form of life-sustaining treatment for at least 7 days. ICU and hospital mortality were 22% and 35%, respectively. For nonsurvivors, the median time from ICU admission to death was 10 days (interquartile range, 3-20 d). Of those who died (n = 5 85), 289 (49%) died while receiving mechanical ventilation, vasopressors, or dialysis. The presence of frailty or advance directives had little impact on limiting use of life-sustaining treatments or shortening the time from admission to death. CONCLUSIONS: In this multicenter study, one third of very elderly ICU patients died in hospital, many after a prolonged ICU stay while continuing to receive aggressive life-sustaining interventions. These findings raise questions about the use of critical care at the end of life for the very elderly.

Prediction scores do not correlate with clinically adjudicated categories of pulmonary embolism in critically ill patients.

BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU). OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients. METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories. RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30). CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.

Early use of supplemental parenteral nutrition in critically ill patients: results of an international multicenter observational study.

OBJECTIVE: To evaluate the effect of using supplemental parenteral nutrition compared to early enteral nutrition alone on nutritional and clinical outcomes. DESIGN: A multicenter, observational study. SETTING: Two hundred twenty-six intensive care units from 29 Countries. PATIENTS: Mechanically ventilated critically ill adult patients that remained in the intensive care unit for >72 hrs and received early enteral nutrition within 48 hrs from admission. INTERVENTIONS: Data were collected on patient characteristics and daily nutrition practices for up to 12 days. Patient outcomes were recorded after 60 days. MEASUREMENTS AND MAIN RESULTS: We compared the outcomes of patients who received early enteral nutrition alone, early enteral nutrition + early parenteral nutrition, and early enteral nutrition + late parenteral nutrition (after 48 hrs of admission). Cox regression analyses were conducted to determine the effect of feeding strategy, adjusted for other confounding variables, on time to being discharged alive from hospital. A total of 2,920 patients were included in this study; 2562 (87.7%) in the early enteral nutrition group, 188 (6.4%) in the early parenteral nutrition group, and 170 (5.8%) in the late parenteral nutrition group. Adequacy of calories and protein was highest in the early parenteral nutrition group (81.2% and 80.1%, respectively) and lowest in the early enteral nutrition group (63.4% and 59.3%) (p < .0001). The 60-day mortality rate was 27.8% in the early enteral nutrition group, 34.6% in the early parenteral nutrition group, and 35.3% in the late parenteral nutrition group (p = .02). The rate of patients discharged alive from hospital was slower in the group that received early parenteral nutrition (unadjusted hazard ratio 0.75, 95% confidence interval 0.59-0.96) and late parenteral nutrition (hazard ratio 0.64, 95% confidence interval 0.51-0.81) (p = .0003) compared to early enteral nutrition. These findings persisted after adjusting for known confounders. CONCLUSIONS: The supplemental use of parenteral nutrition may improve provision of calories and protein but is not associated with any clinical benefit.

Guidelines, guidelines, guidelines: what are we to do with all of these North American guidelines?

Over the past decade, clinical guidelines for nutrition therapy in the critically ill have been developed by different North American societies. To avoid target audience confusion and uncertainty, there is a need to undergo a review of the content of these guidelines. In this review, the authors compared the grading systems, the levels of evidence used, and the content of North American nutrition clinical guidelines. The 3 clinical guidelines that met their search criteria and hence were included in the comparison are the Canadian Clinical Practice Guidelines, the American Dietetics Association's evidence-based guideline for critical illness, and the Society of Critical Care Medicine and American Society of Parenteral and Enteral Nutrition's joint guideline. Through their comparison, the authors have shown that although there are several topics where there is a similar direction of recommendation across the 3 societies/organizations, there are stark contrasts among many of the recommendations. These major differences can be attributed to the admission of different populations, lower levels of evidence or expert opinion into the guideline production process, lack of clarity in the link between the evidence and the recommendation, and lack of uniformity in the reporting of levels of evidence and grades of recommendation. The authors have identified the need for the North American nutrition organizations to harmonize the development of future nutrition guidelines in a timely way, so that they remain current and up-to-date. Furthermore, guideline users need to be aware of the dissimilarities in these guidelines before applying the recommendations to their daily practice.

Nutrition therapy for the critically ill surgical patient: we need to do better!

BACKGROUND: To identify opportunities for quality improvement, the nutrition adequacy of critically ill surgical patients, in contrast to medical patients, is described. METHODS: International, prospective, and observational studies conducted in 2007 and 2008 in 269 intensive care units (ICUs) were combined for purposes of this analysis. Sites provided institutional and patient characteristics and nutrition data from ICU admission to ICU discharge for maximum of 12 days. Medical and surgical patients staying in ICU at least 3 days were compared. RESULTS: A total of 5497 mechanically ventilated adult patients were enrolled; 37.7% had surgical ICU admission diagnosis. Surgical patients were less likely to receive enteral nutrition (EN) (54.6% vs 77.8%) and more likely to receive parenteral nutrition (PN) (13.9% vs 4.4%) (P < .0001). Among patients initiating EN in ICU, surgical patients started EN 21.0 hours later on average (57.8 vs 36.8 hours, P < .0001). Consequently, surgical patients received less of their prescribed calories from EN (33.4% vs 49.6%, P < .0001) or from all nutrition sources (45.8% vs 56.1%, P < .0001). These differences remained after adjustment for patient and site characteristics. Patients undergoing cardiovascular and gastrointestinal surgery were more likely to use PN, were less likely to use EN, started EN later, and had lower total nutrition and EN adequacy rates compared with other surgical patients. Use of feeding and/or glycemic control protocols was associated with increased nutrition adequacy. CONCLUSIONS: Surgical patients receive less nutrition than medical patients. Cardiovascular and gastrointestinal surgery patients are at highest risk of iatrogenic malnutrition. Strategies to improve nutrition performance, including use of protocols, are needed.

Ventilator-associated pneumonia caused by multidrug-resistant organisms or Pseudomonas aeruginosa: prevalence, incidence, risk factors, and outcomes.

PURPOSE: The aim of this study was to clarify the prevalence and incidence of, risk factors for, and outcomes from suspected ventilator-associated pneumonia (VAP) associated with the isolation of either Pseudomonas or multidrug-resistant (MDR) bacteria ("high risk" pathogens) from respiratory secretions. MATERIALS AND METHODS: Data were collected as part of a large, multicentered trial of diagnostic and therapeutic strategies for patients (n = 739) with suspected VAP. RESULTS: At enrollment, 6.4% of patients had Pseudomonas species, and 5.1% of patients had at least 1 MDR organism isolated from respiratory secretions. Over the study period, the incidence of Pseudomonas and MDR organisms was 13.4% and 9.2%, respectively. Independent risk factors for the presence of these pathogens at enrollment were duration of hospital stay >or=48 hours before intensive care unit (ICU) admission (odds ratio, 2.37 [95% CI, 1.40-4.02]; P = .001] and prolonged duration of ICU stay before enrollment (odds ratio, 1.50 [95% CI, 1.17-1.93]; P = .002] per week. Fewer patients whose specimens grew either Pseudomonas or MDR organisms received appropriate empirical antibiotic therapy compared to those without these pathogens (68.5% vs 93.9%, P < .001). The isolation of high risk pathogens from respiratory secretions was associated with higher 28-day (relative risk, 1.59 [95% CI, 1.07-2.37]; P = .04] and hospital mortality (relative risk, 1.48 [95% CI, 1.05-2.07]; P = .05), and longer median duration of mechanical ventilation (12.6 vs 8.7 days, P = .05), ICU length of stay (16.2 vs 12.0 days, P = .05), and hospital length of stay (55.0 vs 41.8 days, P = .05). CONCLUSIONS: In this patient population, the incidence of high-risk organisms newly acquired during an ICU stay is low. However, the presence of high risk pathogens is associated with worse clinical outcomes.

What matters most in end-of-life care: perceptions of seriously ill patients and their family members.

BACKGROUND: Initiatives to improve end-of-life care are hampered by our nascent understanding of what quality care means to patients and their families. The primary purpose of this study was to describe what seriously ill patients in hospital and their family members consider to be the key elements of quality end-of-life care. METHODS: After deriving a list of 28 elements related to quality end-of-life care from existing literature, focus groups with experts and interviews with patients, we administered a face-to-face questionnaire to older patients with advanced cancer and chronic end-stage medical disease and their family members in 5 hospitals across Canada to assess their perspectives on the importance. We compared differences in ratings across various subgroups of patients and family members. RESULTS: Of 569 eligible patients and 176 family members, 440 patients (77%) and 160 relations (91%) agreed to participate. The elements rated as "extremely important" most frequently by the patients were "To have trust and confidence in the doctors looking after you" (55.8% of respondents), "Not to be kept alive on life support when there is little hope for a meaningful recovery" (55.7%), "That information about your disease be communicated to you by your doctor in an honest manner" (44.1%) and "To complete things and prepare for life's end - life review, resolving conflicts, saying goodbye" (43.9%). Significant differences in ratings of importance between patient groups and between patients and their family members were found for many elements of care. INTERPRETATION: Seriously ill patients and family members have defined the importance of various elements related to quality end-of-life care. The most important elements related to trust in the treating physician, avoidance of unwanted life support, effective communication, continuity of care and life completion. Variation in the perception of what matters the most indicates the need for customized or individualized approaches to providing end-of-life care.

End-of-life care in acute care hospitals in Canada: a quality finish?

Understanding patients' and family members' perspectives on the relative importance of elements of end-of-life (EOL) care and their satisfaction with those elements will help prioritize quality improvement initiatives. We administered a face-to-face questionnaire containing a selection of 28 elements of care to eligible inpatients with advanced lung, heart, or liver disease, or metastatic cancer, and available family caregivers (FCGs) in five tertiary care hospitals across Canada. 440 of 569 (78%) eligible patients and 160 of 176 (91%) FCGs participated. No respondent reported complete satisfaction with all elements of care. The average satisfaction score was 4.6 on a 26 point scale. Medical patients reported lower levels of satisfaction than cancer patients. Elements rated as "extremely important" and anything other than "completely satisfied" most frequently by respondents related to discharge planning, availability of home health services, symptom relief, not being a burden, physician trust, and communication. In conclusion, most patients and their family members in our survey were not completely satisfied with EOL care. Improvement initiatives to target key elements identified by patients and FCGs have the potential to improve satisfaction with EOL care across care settings.